DevoTed_miR SIGNED
MicroRNA determinants of the balance between effector and regulatory T cells in vivo
Total Cost €
0EC-Contrib. €
0Partnership
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Project "DevoTed_miR" data sheet
The following table provides information about the project.
| Coordinator |
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Organization address contact info |
| Coordinator Country | Portugal [PT] |
| Project website | https://imm.medicina.ulisboa.pt/pt/investigacao/laboratorios/silva-santos-bruno-lab/ |
| Total cost | 2˙000˙000 € |
| EC max contribution | 2˙000˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-CoG |
| Funding Scheme | ERC-COG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-07-01 to 2020-12-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES | PT (LISBOA) | coordinator | 2˙000˙000.00 |
Map
Project objective
T lymphocytes display potent pro- or anti-inflammatory properties, which typically associate with distinct effector (Teff) versus regulatory (Treg) cell subsets. Based on published and our preliminary data showing a major impact of microRNAs on T cell differentiation and (auto)immune pathology, my proposal aims to dissect the miRNA networks that control the balance between Teff and Treg subsets in vivo, in various experimental models of infection and autoimmunity.
We will focus on three critical mediators of T cell functions: interferon-gamma (IFN-g) and interleukin-17A (IL-17), highly pro-inflammatory Teff cytokines; and Foxp3, the transcription factor that confers Treg suppressive properties. To track the activity of these key genes, we will generate a new Ifng/ Il17/ Foxp3 triple reporter mouse, from which we will isolate Teff and Treg subsets to determine their genome-wide miRNA profiles and specific signatures in vivo. We will investigate both natural (thymic-derived and present in naïve mice) and induced (in the periphery upon challenge) Teff and Treg subsets, as they make distinct contributions to the immune response. We will identify miRNAs selectively expressed in Teff (Ifng or Il17) versus Treg (Foxp3) subsets of various lineages (CD4, CD8, gamma-delta or NKT) in each in vivo model; assess whether they are induced during thymic development or upon peripheral activation; and determine the robustness of subset-specific miRNA profiles across various in vivo challenges.
We will then use loss- and gain-of-function strategies to define the individual miRNAs that impact Teff or Treg differentiation and disease pathogenesis; dissect the external cues and intracellular mechanisms that regulate miRNA expression; and identify the mRNA networks controlled by key miRNAs in Teff and Treg differentiation. I expect this project to provide major conceptual and experimental advances towards manipulating miRNAs either to boost immunity or to treat autoimmunity.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Bruno Silva-Santos, Sofia Mensurado, Seth B. Coffelt γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer published pages: 392-404, ISSN: 1474-175X, DOI: 10.1038/s41568-019-0153-5 |
Nature Reviews Cancer 19/7 | 2020-01-24 |
| 2019 |
Francisco Caiado, Diogo Maia-Silva, Carolina Jardim, Nina Schmolka, Tânia Carvalho, Cláudia Reforço, Rita Faria, Branka Kolundzija, André E. Simões, Tuncay Baubec, Christopher R. Vakoc, Maria Gomes da Silva, Markus G. Manz, Ton N. Schumacher, Håkan Norell, Bruno Silva-Santos Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-12983-z |
Nature Communications 10/1 | 2020-01-24 |
| 2019 |
Julie C. Ribot, Rita Neres, Vanessa Zuzarte-LuÃs, Anita Q. Gomes, Liliana Mancio-Silva, Sofia Mensurado, Daniel Pinto-Neves, Miguel M. Santos, Tânia Carvalho, Jonathan J. M. Landry, Eva A. Rolo, Ankita Malik, Daniel Varón Silva, Maria M. Mota, Bruno Silva-Santos, Ana Pamplona γδ-T cells promote IFN-γ–dependent Plasmodium pathogenesis upon liver-stage infection published pages: 201814440, ISSN: 0027-8424, DOI: 10.1073/pnas.1814440116 |
Proceedings of the National Academy of Sciences | 2020-01-24 |
| 2019 |
Miguel Ribeiro, Helena C. Brigas, Mariana Temido-Ferreira, Paula A. Pousinha, Tommy Regen, Cátia Santa, Joana E. Coelho, Inês Marques-Morgado, Cláudia A. Valente, Sara Omenetti, Brigitta Stockinger, Ari Waisman, Bruno Manadas, LuÃsa V. Lopes, Bruno Silva-Santos, Julie C. Ribot Meningeal γδ T cell–derived IL-17 controls synaptic plasticity and short-term memory published pages: eaay5199, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aay5199 |
Science Immunology 4/40 | 2020-01-24 |
| 2016 |
A. R. Almeida, D. V. Correia, A. Fernandes-Platzgummer, C. L. da Silva, M. G. da Silva, D. R. Anjos, B. Silva-Santos Delta One T Cells for Immunotherapy of Chronic Lymphocytic Leukemia: Clinical-Grade Expansion/Differentiation and Preclinical Proof of Concept published pages: 5795-5804, ISSN: 1078-0432, DOI: 10.1158/1078-0432.ccr-16-0597 |
Clinical Cancer Research 22/23 | 2020-01-24 |
| 2018 |
Sofia Mensurado, Margarida Rei, Telma Lança, Marianna Ioannou, Natacha Gonçalves-Sousa, Hiroshi Kubo, Marie Malissen, Venizelos Papayannopoulos, Karine Serre, Bruno Silva-Santos Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress published pages: e2004990, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.2004990 |
PLOS Biology 16/5 | 2020-01-24 |
| 2018 |
Nina Schmolka, Pedro H. Papotto, Paula Vargas Romero, Tiago Amado, Francisco J. Enguita, Ana Amorim, Ana F. Rodrigues, Katrina E. Gordon, Ana S. Coroadinha, Mark Boldin, Karine Serre, Amy H. Buck, Anita Q. Gomes, Bruno Silva-Santos MicroRNA-146a controls functional plasticity in γδ T cells by targeting NOD1 published pages: eaao1392, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aao1392 |
Science Immunology 3/23 | 2020-01-24 |
| 2018 |
Duncan R. McKenzie, Iain Comerford, Bruno Silva-Santos, Shaun R. McColl The Emerging Complexity of γδT17 Cells published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00796 |
Frontiers in Immunology 9 | 2020-01-24 |
| 2018 |
Daniel P. Inácio, Tiago Amado, Bruno Silva-Santos, Anita Q. Gomes Control of T cell effector functions by miRNAs published pages: 63-73, ISSN: 0304-3835, DOI: 10.1016/j.canlet.2018.04.011 |
Cancer Letters 427 | 2020-01-24 |
| 2017 |
Miguel Muñoz-Ruiz, Nital Sumaria, Daniel J. Pennington, Bruno Silva-Santos Thymic Determinants of γδ T Cell Differentiation published pages: 336-344, ISSN: 1471-4906, DOI: 10.1016/j.it.2017.01.007 |
Trends in Immunology 38/5 | 2020-01-24 |
| 2017 |
Bruno Silva-Santos, Jessica Strid γδ T cells get adaptive published pages: 370-372, ISSN: 1529-2908, DOI: 10.1038/ni.3705 |
Nature Immunology 18/4 | 2020-01-24 |
| 2017 |
Pedro H Papotto, Julie C Ribot, Bruno Silva-Santos IL-17+ γδ T cells as kick-starters of inflammation published pages: 604-611, ISSN: 1529-2908, DOI: 10.1038/ni.3726 |
Nature Immunology 18/6 | 2020-01-24 |
| 2018 |
Pedro H. Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases published pages: 26-37, ISSN: 0896-8411, DOI: 10.1016/j.jaut.2017.11.006 |
Journal of Autoimmunity 87 | 2020-01-24 |
| 2017 |
Nital Sumaria, Capucine L. Grandjean, Bruno Silva-Santos, Daniel J. Pennington Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells published pages: 2469-2476, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2017.05.071 |
Cell Reports 19/12 | 2020-01-24 |
| 2017 |
Hiroshi Kubo, Sofia Mensurado, Natacha Gonçalves-Sousa, Karine Serre, Bruno Silva-Santos Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK Cells published pages: 812-820, ISSN: 2326-6066, DOI: 10.1158/2326-6066.CIR-17-0082 |
Cancer Immunology Research 5/9 | 2020-01-24 |
| 2017 |
Pedro H Papotto, Natacha Gonçalvesâ€Sousa, Nina Schmolka, Andrea Iseppon, Sofia Mensurado, Brigitta Stockinger, Julie C Ribot, Bruno Silvaâ€Santos ILâ€23 drives differentiation of peripheral γδ17 T cells from adult bone marrowâ€derived precursors published pages: 1957-1967, ISSN: 1469-221X, DOI: 10.15252/embr.201744200 |
EMBO reports 18/11 | 2020-01-24 |
| 2016 |
Miguel Muñoz-Ruiz, Julie C Ribot, Ana R Grosso, Natacha Gonçalves-Sousa, Ana Pamplona, Daniel J Pennington, José R Regueiro, Edgar Fernández-Malavé, Bruno Silva-Santos TCR signal strength controls thymic differentiation of discrete proinflammatory γδ T cell subsets published pages: 721-727, ISSN: 1529-2908, DOI: 10.1038/ni.3424 |
Nature Immunology 17/6 | 2020-01-24 |
| 2016 |
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos Casein kinase 2 controls the survival of normal thymic and leukemic γδ T cells via promotion of AKT signaling published pages: , ISSN: 0887-6924, DOI: 10.1038/leu.2016.363 |
Leukemia | 2020-01-24 |
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